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Zika: The new global health terror

In the Zika forest of Uganda, in April 1947, a rhesus monkey developed a fever. The monkey was caged on a tree platform, part of a U.S. research program investigating tropical diseases. Two days later, the feverish monkey was brought to a lab in the town of Entebbe, where its blood serum was injected into mice. After 10 days, all the mice were sick too. This was the first recorded appearance of the Zika virus, which was later found in mosquitoes trapped in the same forest, according to a 2009 article in the journal Emerging Infectious Diseases. Scientists learned that these mosquitoes could spread the virus to humans, but the symptoms are generally mild, and last only up to a week: they include fever, rash, joint pain and red eyes. In fact, only one in five infected people show any symptoms at all. For the next 60 years or so, the Zika virus was more or less forgotten.

Less than a year ago, Zika was reported in Brazil. As more people were infected, evidence began to emerge that this virus might not be so harmless at all. Officials started to suspect that pregnant women who are bitten by an infected mosquito might be more likely to give birth to infants with brain damage and abnormally small heads, a condition called microcephaly. Other people are apparently at risk of developing Guillain-Barré syndrome, which can cause temporary paralysis and, in rare instances, death. Scientists have yet to definitively link either condition to Zika infection, but such a link looks increasingly likely. Before they had a chance to fully understand the virus’s impact, the number of cases started growing out of control.

In recent months, the Zika virus has ripped through the Americas like wildfire, sparking a pandemic that nobody saw coming. Zika has gone “from a mild threat to one of alarming proportions,” says World Health Organization director-general Margaret Chan, who warned that it is spreading “explosively” through the region. With up to 1.5 million cases in Brazil alone, the WHO predicts there could soon be up to four million people infected across the Americas. (By contrast, a total of 8,098 people worldwide became sick during the 2003 outbreak of severe acute respiratory syndrome, or SARS.)

Solange Ferreira bathes her son at her house in Brazil; reported cases of microcephaly there have climbed to 4,180 since October. (Felipe Dana/AP)

As of Feb. 2, Zika was transmitting locally in 26 countries and regions in Central and South America and the Caribbean, including Mexico, Barbados and Puerto Rico—places where, a year ago, it had never been seen. The WHO predicts that it will spread to all regions in the Americas, except for Canada and continental Chile, where the type of mosquito that carries it can’t survive. They say it might also reach areas in Africa, Asia and southern Europe. There’s currently no Zika vaccine, no treatment, no cure.

There’s new evidence that mosquitoes might not be the only ones responsible for its spread. On Feb. 2, health officials in Dallas County, Texas, reported the first locally acquired case of the Zika virus on U.S. soil in the current outbreak—a person who was infected sexually, by someone who was sick with Zika after a trip to Venezuela. So far, there’s only been limited evidence that Zika could be transmitted sexually. If more cases like this are reported, that will change the nature of the threat once more.

Public health officials’ mounting panic was evident in the wave of warnings issued shortly after the new year, each more tensely worded than the last. On Jan. 15, the U.S. Centers for Disease Control (CDC) issued an unprecedented advisory, instructing pregnant women not to travel, if at all possible, to 14 Zika-affected countries and regions. Days later, they added eight more to the list, like Ecuador; Cape Verde, off the coast of Africa; and Samoa, in the South Pacific. Nigeria has issued a travel restriction to Latin America, aimed at pregnant women. In the U.K., authorities told couples returning from these areas to avoid getting pregnant for at least a month, while they might unknowingly be infected. And Canadians coming home from the region have been told not to donate blood for one month, in case they’re carrying the virus.

On Feb. 1, the WHO took the rare step of naming Zika a “public health emergency of international concern.” A political manoeuvre intended to direct money and resources—and especially attention—at the crisis, it should spur efforts to halt the virus’s spread. In declaring the public health emergency, the WHO cited “the recent cluster of microcephaly cases,” and advised pregnant women to consider delaying travel to affected areas. It stopped short of making any travel or trade restrictions, although some critics attacked the agency for not warning pregnant women off visiting affected countries.

Aedes aegypti mosquitos are seen in containers at a lab of the Institute of Biomedical Sciences of the Sao Paulo University, on January 8, 2016 in Sao Paulo, Brazil. Researchers at the Pasteur Institute in Dakar, Senegal are in Brazil to train local researchers to combat the Zika virus epidemic. (NELSON ALMEIDA/AFP/Getty Images)

Still, a growing number of would-be travellers are changing plans. Air Canada and other airlines recently said they’d allow passengers to change or cancel bookings to regions where Zika is spreading. The pandemic sprang to life so quickly that others have been caught off-guard. Travellers returning to Australia, Denmark, Israel and the U.S. have since been diagnosed with Zika. Here in Canada, as of Feb. 2, six cases of infection had been reported: two in B.C., one in Alberta, and three in Quebec. All six had recently visited either Brazil, El Salvador, Colombia or Haiti, according to the Public Health Agency of Canada. At least one baby in the U.S. has been born with microcephaly. The child’s mother was in Brazil early in her pregnancy.

For those who live where the Zika virus is circulating, the situation looks even more stark. The fear of birth defects is so great that authorities in Colombia, El Salvador, Jamaica and Ecuador have reportedly urged women not to get pregnant for now. With no treatments that stop the virus, doctors’ best advice is to avoid mosquito bites, to use bug repellent and to stay indoors. For now, there is no end in sight. “It is a pandemic,” says Brian Ward, a professor of medicine and microbiology at McGill University, and an expert in tropical diseases. “We are on the upslope.”

More clouds are gathering on the horizon. In August, Brazil hosts the Summer Olympics, and half a million tourists are expected to visit. The country plans to deploy 220,000 military troops to go door-to-door and speed eradication efforts. Incredibly, Brazil is warning pregnant women not to attend. “The risk, which I would say is serious, is for pregnant women. It is clearly not advisable for you [to travel to Brazil for the Games] because you don’t want to take that risk,” said Jaques Wagner, President Dilma Rousseff’s chief of staff. But the risk to others is not so serious, he continued, and insisted that the Olympics will not be cancelled.

In the southern U.S., where no local transmission by mosquito has been reported to date, people are bracing for springtime, when the bugs become more active. The Aedes aegypti species, which carries Zika, can be found in Florida and along the Gulf Coast. “If you have a generation of pregnant women terrified of going outside,” says Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, “that’s going to be a game-changer.”

Zika is spreading so rapidly—and seems to have such devastating effects—that experts speculate the virus may have mutated, and taken on a far more dangerous form.

Scientists don’t know how Zika made its way to the Americas, halfway around the world from where it was discovered. It seems to have hopped eastwards along islands that dot the Pacific. An isolated outbreak was reported on the tiny South Pacific island of Yap, in 2007, and another in French Polynesia in 2013. There, 11 per cent of the population was affected. But not many people live on those islands, and Zika’s effects—which are mild in most people—didn’t raise flags.

The virus arrived in Easter Island, off the coast of South America, and then came to Brazil. That country has plenty of disease-carrying mosquitoes, and a massive population of 200 million—the vast majority with little or no immunity to Zika, like almost everyone else in the Americas. Brazilian public officials first reported local transmission of the virus in May 2015. “There wasn’t very much concern about it,” Ward says. “Compared to dengue and chikungunya,” two other mosquito-borne illnesses in the area, he says, “Zika is a weenie.” At least, that’s what authorities believed at the time.

As the number of infections grew, officials noticed something chilling: a twentyfold increase in babies born with microcephaly, a rare and devastating birth defect. “Microcephaly is not subtle. It’s very severe,” says Kellie Murphy, a maternal-fetal medicine specialist at Toronto’s Mount Sinai Hospital. The outcomes of these babies vary widely. Some will struggle to feed themselves, and have a shortened lifespan. (No Canadian cases of Zika-linked microcephaly have been reported. Maternal infections with viruses like rubella, or chromosomal disorders, can also cause the condition.)

On Jan. 27, health authorities in Brazil said that, since Oct. 4, 180 cases of suspected microcephaly had been reported. (Brazil typically sees about 150 cases per year.) After over 700 reports were examined, microcephaly was confirmed in 270 of them—and in six of those, there was evidence of Zika. Researchers discovered the virus in the amniotic fluid of two pregnant women, whose fetuses were diagnosed with microcephaly via ultrasound. The CDC found traces in the brains of two newborns with microcephaly who died, and in the placentas of two women who miscarried fetuses with the condition.

“Retrospectively, in French Polynesia, we’re seeing evidence that [microcephaly] may have been happening there, too,” says Scott Weaver, director of the Institute for Human Infections and Immunity at the University of Texas Medical Branch. But the population there is so much smaller, it was harder to notice. Weaver and his team are trying to develop a lab animal that can be used as a research model of Zika infection, to understand how the virus might contribute to microcephaly. It could take several more months of work, WHO officials say, before a link between Zika and microcephaly is confirmed.

At this time of year, Canadians would typically be flocking south. Spooked travellers are starting to reconsider. “I certainly can’t recall another situation where airlines were so willing to offer a refund due to an outbreak,” travel blogger Chris Myden says in an email. “They’re generally reluctant to give refunds for any reason.”

In late January, Myden started to notice some chatter about Zika on his Facebook pages, which feature deals on flights and travel packages from Canada. On the Edmonton page, one woman wrote: “Any thoughts on the Zika virus?” She’d planned to visit the Bahamas (which is not currently on the list of affected regions) with a pregnant friend. Confusion reigned. One poster accused the media of “massively overblowing” the Zika pandemic. Another poster told her she should go, but not let her friend outside. Others suggested wearing lots of bug spray, but one woman wrote: “Diligence with repellent is not enough. I was eaten alive in Australia a few weeks ago despite using 80 per cent DEET religiously—they’ll find a spot.” Said another: “Have a great time, drink too much, get lots of sunshine and don’t worry about it.”

If would-be travellers are confused, imagine those who’ve recently visited a place where Zika is spreading. They have to cope with a frustrating lack of information. There is no commercially available test for Zika. Canada’s Public Health Agency has a test that can detect the virus in a patient’s blood up to two weeks after infection. If a pregnant woman travelled earlier on, that test won’t be of much use. (The agency, which is working to build testing capacity, says it can send away for further tests to the CDC if necessary.) “Ideally, it would be great to check [a patient’s] blood and say, ‘You’re not at risk,’ ” says Murphy, the Mount Sinai obstetrician. “But we’re not there yet.”

Canadian doctors are following the CDC’s advice to pregnant women, but it’s vague. If the woman has no symptoms, but has visited an area where Zika is circulating, the CDC says that her doctor should follow the fetus regularly via ultrasound to look for signs of microcephaly. The condition is best diagnosed late in the second trimester and beyond; but the accuracy of this method in detecting microcephaly related to Zika “is not known,” the CDC says, adding that better guidelines will be drafted when we know more. Women with symptoms of Zika should be tested, the CDC says, but that doesn’t address the four-in-five who won’t show any. Doctors can’t say for sure if their fetuses will be affected. Neither Canada nor the U.S. currently has the capacity for general screening. “You’d be scaring a huge number of people unnecessarily,” Ward says. “If there were something we could do about it, maybe I’d feel differently.”

Many women who have contracted Zika seem to have healthy babies. For a person who tests positive, health authorities’ best recommendations are rest, drink ﬂuids and take acetaminophen to reduce pain and fever.

Those early in their pregnancies, especially in the first trimester, are probably most vulnerable, but even that’s not definitive—which is why Lyle Petersen, the CDC’s director of vector-borne diseases, said that pregnant women “in any trimester” should avoid visiting a region where Zika is transmitting. “We do not know exactly what is the biggest period of risk during a woman’s pregnancy,” he said. “This is a new situation. It’s a dynamic situation. I think we’re just going to have to wait and see how this all plays out.”

The CDC guidelines are “confusing,” says Hotez. “Too much is left for the layperson to interpret.” And they’re cold comfort to people living in Brazil, El Salvador, Colombia and other areas where the virus has taken hold. They face the harrowing prospect of putting off pregnancy, or having a child with a lifelong disability. Some countries in the region ban abortion outright. In El Salvador, women suspected of having an abortion can face criminal charges and jail time.

Brazil’s health minister, Marcelo Castro, has said that his country is “badly losing” the battle against disease-spreading mosquitoes, and that the Zika outbreak is probably worse than it looks because so many infected people don’t exhibit symptoms. As part of its efforts, Brazil plans to distribute mosquito repellent to some 400,000 pregnant women.

The link to Guillain-Barré syndrome is just as mysterious and fear-inducing, although scientists can say even less about it than the suspected link to microcephaly, not even who might be at risk. Brazil’s health ministry and others have reported a worrying increase in cases of Guillain-Barré, which arises when the body’s immune system attacks the nervous system. It was called “more terrifying than any horror movie” by one young Brazilian woman, who spoke to the New York Times. Infected with Zika by a mosquito bite, she was paralyzed and had to be put on a ventilator in the intensive care unit.

The scariest part is how little we understand the virus. “Nothing about this epidemic has been published. Nothing has been peer reviewed,” says Hotez. “It’s all coming through WHO alerts and anecdote.”

TOPSHOT – A municipal agent sprays anti Zika mosquitos chimical product at the sambadrome in Rio de Janeiro, on January 26, 2016.Brazil is mobilizing more than 200,000 troops to go “house to house” in the battle against Zika-carrying mosquitoes, blamed for causing horrific birth defects in a major regional health scare, a report said Monday. (CHRISTOPHE SIMON/AFP/Getty Images)

One of the most perplexing questions is—why has this “weenie” of a virus, as Ward calls it, started to flex its muscle? Zika has circulated in parts of Africa and Asia for decades at least. If there was any chance it could lead to such disastrous outcomes, even in just a small number of people who are infected, why wouldn’t we know about it?

For now, scientists can only speculate. It could be that people in parts of Africa and Asia have been exposed to Zika and other viruses like it from childhood on, so they’ve built up an immunity, and consequently, infection rates stay low. “Zika is there, but it’s not causing pandemics,” Ward says. “It’s part of the background noise.” (In the 1950s, researchers tested people in India for the Zika virus, and found that many had antibodies in their blood, suggesting they’d previously been infected and recovered.) Another possibility is that Zika’s more serious side effects have always existed, but health officials didn’t notice because they occurred at regular intervals, not in the sudden burst we’ve seen in the Western hemisphere. Once the virus hit the Americas, where millions had never been exposed to Zika before, so many were infected so rapidly that previously rare events were starkly obvious.

Weaver, who’s studied mosquito-borne viruses his entire career, is considering another explanation. “It’s possible the Zika virus has mutated,” Weaver says. “That’s what we’ve seen in chikungunya,” another mosquito-borne virus that recently spread from Africa to Europe and the Americas. Chikungunya causes fever and joint pain, and “makes you feel absolutely miserable,” says Ward. “Some people get permanent arthritis,” and can’t work or function normally. About one in 1,000 cases is fatal.

Chikungunya—like Zika, dengue and yellow fever—is transmitted by the Aedes aegypti mosquito, which is notorious to public health authorities. A small, dark insect, it feeds on humans (it will sometimes bite animals), and strikes mostly in the day. It lays eggs in standing water, so it’s found near human settlements, and likes to come indoors.

According to the CDC, this species of mosquito sneaks up on its victims, approaching from behind, and biting ankles and elbows: people sometimes won’t even realize they’ve been bitten. The Aedes aegypti mosquito lives across Central and South America and the Caribbean, all the way up into Florida and the U.S. Gulf Coast. It doesn’t come as far north as Canada, although its relative, Aedes albopictus, ranges to Chicago and New York in the summertime. (There is some evidence that Aedes albopictus might transmit Zika, but less effectively.) According to Weaver, the chikungunya virus mutated to be carried by Aedes albopictus more efficiently, and has spread more rapidly through the Americas as a result.

Zika might have undergone a similar transformation. “Maybe somewhere along the way, it became more efficient at infecting mosquitoes. Or maybe it adapted for more efficient replication in humans,” Weaver says. That could explain why it might be causing such alarming new effects—and why it’s tearing through the Americas. “It’s also possible the virus became better capable of crossing the placenta, into the fetus.”

Patient Sandra Milena Ovallos, 20 years old and 25 weeks pregnant, attends a medical examination after suffering from fever and skin rash at the Hospital Universitario Erazmo Meoz in Cucuta, Colombia. (Schneyder Mendoza/EPA/CP)

Kamran Khan, of St. Michael’s Hospital in Toronto, studies the spread of infectious disease as it relates to globalization. He became interested during the SARS epidemic of 2003. SARS was first diagnosed in a Toronto woman who’d returned from Hong Kong. A total of 44 people in Canada died in that outbreak, and an astounding 25,000 were placed under quarantine. “The world has become so much smaller,” Khan says. “Clinicians have to think about diseases that occur not just in our backyard, but anywhere in the world.”

We’re far more interconnected now, only a decade after SARS. According to Khan, 3.5 billion trips are made on commercial flights every year. A virus like Zika could travel with an infected passenger on any one of those flights, landing in a new location. Once home, if an infected person is bitten by an uninfected mosquito that can carry the virus, that bug can become infected, and spread it to another person—and the virus moves on and on. For that reason, the CDC says that any infected person should be careful not to get any additional mosquito bites for at least a week, to avoid infecting more mosquitoes.

Now, with the new report that a person in Texas has acquired the virus sexually, public health officials will be focused on another way it can spread. There’s only been limited evidence that Zika was transmissible by sex, amounting to two case studies. During the 2013 outbreak in French Polynesia, a man in Tahiti fell ill, and the virus was isolated from his semen. The other case, reported in 2008, was a U.S. researcher, infected with Zika while on a trip to Senegal. He returned to Colorado, and experienced the symptoms associated with Zika infection. So did his wife, but she had not been to Senegal, or anywhere outside of the U.S., although they had sex a day after he came home.

“There’s very little information right now [on possible sexual transmission],” says Teresa Tam, Canada’s deputy chief public health officer. The agency is working to develop some kind of guidelines, she explains. Until then, “precautionary measures might be appropriate.” (Dallas County health officials now recommend condoms, in addition to mosquito protection.) As for whether it can be transmitted by blood transfusion, that, too, isn’t totally clear. According to Tam, in another study in French Polynesia, three per cent of asymptomatic blood donors were carrying the Zika virus in their blood, which is why restrictions were placed on blood donors here.

As scientists work to untangle all this, Zika moves further afield. Khan is the author of a paper in The Lancet that examines how Zika could spread even further. He and his team mapped the final destinations of international travellers leaving airports in Brazil, from September 2014 to August 2015. Of 9.9 million travellers, they found, 65 per cent were going to the Americas, 27 per cent to Europe, and five per cent to Asia. (The greatest number were headed to the U.S.) A team from Oxford University mapped the global spread of the Aedes mosquito, and modelled climate conditions that allow the virus to spread from mosquito to human. More than 60 per cent of the U.S. population, they found, live in areas where seasonal transmission is possible. Almost 23 million Americans are in climate zones where Zika can be transmitted year-round.

Hotez remembers the Ebola scare in 2014, and panic after a health care worker in his state was diagnosed with the virus. (Ebola, which is transmitted through contact with bodily fluids, infected just a handful of Americans, although it ravaged West Africa.) At the time, he was a voice of reassurance to Texans who feared that Ebola would spread there. “I was on TV a lot, and explained why Ebola will never gain a foothold here,” says Hotez. “I’m not saying that now. I’m very concerned.”

Staring down a pandemic expected to hit the U.S., Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, recently told Time he wants a “full-court press” for a Zika vaccine. “I’m saying, ‘Folks, this is it, all hands on deck for Zika, this is really important.’ ”

The tone of public health officials is much different than it was in the early days of Ebola. Then, the WHO was criticized for dragging its feet: it didn’t declare Ebola a global public health emergency until months after alarms had been sounded, and nearly 1,000 people in West Africa had died. Drug makers were chastized for not more aggressively pursuing a vaccine. “The technology to make an Ebola vaccine was published in 2003,” says Hotez, president of the non-profit Sabin Vaccine Institute. “It sat on the shelf for more than a decade, because the model says, you wait for big pharma to license it and turn it from a discovery into a product.” Taking a drug to market can cost hundreds of millions of dollars, which is beyond the reach of research labs. In 2014, Margaret Chan of the WHO castigated the pharmaceutical industry for ignoring the plight of Africans who suffered from Ebola. “A profit-driven industry does not invest in products for markets that cannot pay,” she said.

Weaver believes that experimental Zika vaccines will begin to roll out in short order. “The challenge is, will there be enough commercial interest for a company to invest in one?” he wonders, especially as more people develop immunity to Zika, and the pandemic ebbs. He does believe there will be a market for a vaccine, “because microcephaly is such a frightening outcome.” Not to mention that Zika is sweeping through the Americas, close to home.

Scientists are racing to make a vaccine, and an early front-runner has a Canadian connection. Gary Kobinger, head of special pathogens at the Public Health Agency’s National Microbiology Lab in Winnipeg (who was also behind an Ebola vaccine and the Ebola drug ZMapp), believes their Zika vaccine could be ready for human clinical trials as early as this summer. Even so, “it could be years before there’s widespread access,” he says.

Doctors also need a better test for the virus, to identify who’s been infected. Tom Hobman, a professor in the department of cell biology at the University of Alberta, is working on a version that’s cheap and effective, to be deployed in Central and South America. The one used today is “very sensitive, and highly specific, but more expensive and needs specialized equipment,” he explains. “If you’re looking at millions of infections, that’s not the best way to go.” His test will be designed to provide results for Zika within a couple of hours, based on a blood sample.

Curbing the spread of this virus means getting rid of mosquitoes, which has been done before. In the 20th century, as dengue swept South America, governments made it a priority to eliminate Aedes aegypti, fumigating and destroying habitats, says a paper in The American Journal of Tropical Medicine and Hygiene. In 1962, 18 continental countries and many Caribbean islands announced they’d wiped out the Aedes, but measures must be kept up to stay effective, which takes money and political will. From the 1970s to the 1990s, Aedes aegypti returned, as did dengue fever and other mosquito-borne diseases—with consequences that are now all too apparent.

Scientists have begun toying with more high-tech solutions. A British company, Oxitec, has experimented with genetically modified mosquitoes whose offspring die before they reach adulthood, causing populations to crash. In the U.S., researchers have made “malaria-proof” mosquitoes, which pass along a malaria-blocking gene to nearly all their offspring. Some suggest these techniques could be used to stop bugs from transmitting viruses like Zika, or even to wipe out the Aedes aegypti for good. But once the genie is out of the bottle and these mutant mosquitoes begin to spread, there’s no taking it back. Even in the face of a global pandemic, scientists are right to be cautious.

Over the last weekend of January, as many as 300,000 people gathered in the streets of Rio de Janeiro to celebrate Carnival, which was then still days away. Officials were busy fumigating the city stadium, where tourists and locals were expected to gather. In anticipation of the Olympics, authorities say they’ll perform inspections of facilities, and destroy mosquito breeding grounds. It’s too early to tell what sort of chilling effect Zika will have on tourism there, not to mention Mexico and the Caribbean, although we know that SARS cost Ontario hoteliers $60 million in the month of April 2013 alone.

As for the U.S., “if Zika is going to hit the Gulf Coast,” Hotez predicts, “it will be around April.” Those who live in poor communities will be hardest-hit. Dengue, a major cause of illness and death in the tropics, has shown up in economically depressed parts of Houston. “You have dilapidated housing, ripped screens or no screens at all, and environmental degradation around the house, garbage piled up, standing water,” Hotez says.

In Canada, it’s easy to feel complacent. Health officials emphasize that our risk is low, and that’s true: even if a handful of travellers bring Zika home, it can’t be transmitted without lots of Aedes mosquitoes to spread it around. But the climate is changing, and bugs are ranging farther north—the Aedes albopictus, which might be able to transmit Zika, can already make it to Chicago in the summertime, so it’s hard to believe it’s not here, at least in extremely limited numbers. “The problem of climate change is very much related to Zika,” Khan says. “Many of these diseases originate in animals, whether it’s HIV, SARS, Ebola”—or Zika.

One of the most frightening aspects of the Zika pandemic is how unprepared we’ve been. Yet we’ve known about this virus for 60 years, because of a research program in the forests of Uganda. According to Weaver, money for that type of work has mostly dried up. Until recently, it would have been “very difficult” to get funding to study Zika, he says.

The simplest way to stop a pandemic is to do so before it catches fire. “We need to invest in the surveillance and discovery of new viruses,” Weaver emphasizes, “to know what the next threat might be.” Experts worry that, even in the midst of this global Zika panic, that’s unlikely to change.